Statin-induced Myopathy Research Articles

State of the Art Comprehensive Review of Individual Statins, Their Differences, Pharmacology, and Clinical Implications.

Statins are currently the primary treatment for hyperlipidemia, particularly for the treatment of high levels of low-density lipoprotein cholesterol (LDL-C), as many studies have proven benefit in a variety of populations. The benefits of statin treatment for high cholesterol have been proven in many trials. Forefront among different adverse events is statin-induced myopathy, which still eludes complete understanding, and may range anywhere from muscle soreness or fatigue to potentially extremely rare occurrence of rhabdomyolysis.As most adverse events are rare and not life-threatening, in high-risk patients, a high-dose statin should be started initially as data suggests that clinicians rarely up titrate statin therapy after initial prescription leading to under-treatment of many patients requiring high-dose statin therapy. As we will discuss in this paper, musculoskeletal side effects are the main concern and reason for discontinuing statin therapy. The occurrence and true association of other adverse events in patients on statin such as new onset of diabetes, hepatic toxicity, or cognitive impairment are rare, controversial, and not proven. In placebo-controlled studies, abnormal liver function occurs to a similar degree in statin- and placebo-treated patients. This led to FDA removal of the requirement to monitor liver function tests in patients on statin therapy.The combination of statins with other compounds such as ezetimibe or PCSK9 inhibitors has shown some additional benefits in the treatment of hypercholesterolemia. The goal of this manuscript is to conduct a comprehensive review about most commonly usedstatins and compare data on their history, structures, benefits, adverse effects, and clinical outcomes.

P821Treatment patterns of lipid lowering therapy in patients with coronary artery disease above vs. below 75 years of age

Abstract Introduction In patients with coronary artery disease (CAD), lipid lowering therapy is recommended as cornerstone of secondary prevention. Treatment of elderly patients inherits a medical challenge, as they experience higher absolute risk reduction with more intensive lipid lowering regimes but may be more prone to side effects by therapy. Purpose To evaluate the treatment patterns in lipid lowering therapy comparing CAD-patients above vs. below 75 years of age. Methods We retrospectively included patients with known CAD, admitted to the West German Heart and Vascular Center in the years of 2009–2010 (n=500), 2012–2013 (n=500), and 2015–2016 (n=500). LDL-cholesterol levels and intensity of stain therapy (based on dosage and type of statin) were assessed from all available hospital records. Lipid levels and treatment regimens were evaluated comparing patients ≥75 vs. <75 years of age. The analysis was approved by the local ethics committee (17–7458-BO). Results A total of 1,500 patients (mean age: 68.4±11.2 years, 75.8% male) from 813 referring treating primary care physicians in 98 cities of Germany were included in our analysis. 983 patients were <75, whereas 517 were ≥75 years of age. Elderly patients were less likely male (67.9% vs. 79.9%, p<0.0001), had lower BMI (26.8kg/m2 vs. 28.4kg/m2, p<0.0001), and less likely current smokers (7.6% vs. 19.2%, p<0.0001, for patients ≥75 vs. <75 years of age, respectively). LDL-cholesterol levels were not significantly different between age groups (≥75: 96.1±35.1 mg/dl; <75: 98.9±35.7mg/dl, p=0.14). In contrast, elderly patients had higher HDL-cholesterol levels (49.9±15.1 mg/dl vs. 46.7±15.2, p=0.0002) and markedly lower triglycerides (135.6±90.0mg/dl vs. 171.4±124.6mg/dl, p<0.0001). Simvastatin was most frequently prescribed in both age groups (54.9% vs. 50.7%, p=0.16), followed by Atorvastatin (31.6% vs. 33.3%, p=0.53). Elderly patients received significantly lower dosages of statin (28.8±12.8mg vs. 31.4±13.7mg, p=0.0007). Interestingly, patients ≥75 years of age archived LDL<70mg/dl slightly more frequently than younger patients (24.0% vs. 20.1%, p=0.09). Excluding patients with myocardial infarction at presentation, CK-levels were not relevantly different between age groups (131.9±450.0U/l vs. 127.5±111.4U/l, p=0.78). Excluding patients with signs of systemic inflammation, high-sensitive CRP levels did not differ when comparing patients ≥75 vs. <75 years of age (0.15±0.12mg/dl vs. 0.14±0.12mg/dl, p=0.33). Conclusion Evaluating lipid lowering treatment patters of 1500 patients from 813 treating physicians, we observed that patients ≥75 years of age receive lower doses of statin therapy, but reached slightly lower LDL-cholesterol-levels. However, the majority of elderly patients miss current recommendations regarding LDL-thresholds. Interestingly, no signs of a higher frequency of statin-induced myopathy in the elderly were observed in our analysis.

Creatine as a Candidate to Prevent Statin Myopathy.

Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency might be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine; thus, they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of ATP would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of the mitochondrial permeability transition pore that is caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elderly individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.

Prediction of pharmacokinetic drug-drug interactions causing atorvastatin-induced rhabdomyolysis using physiologically based pharmacokinetic modelling

Atorvastatin and its lactone form metabolite are reported to be associated with statin-induced myopathy (SIM) such as myalgia and life-threatening rhabdomyolysis. Though the statin-induced rhabdomyolysis is not common during statin therapy, its incidence will significantly increase due to pharmacokinetic drug-drug interactions (DDIs) with inhibitor drugs which inhibit atorvastatin’s and its lactone’s metabolism and hepatic uptake. Thus, the quantitative analysis of DDIs of atorvastatin and its lactone with cytochrome P450 3A4 (CYP3A4) and organic anion-transporting polypeptide (OATP) inhibitors is of great importance. This study aimed to predict pharmacokinetic DDIs possibly causing atorvastatin-induced rhabdomyolysis using Physiologically Based Pharmacokinetic (PBPK) Modelling. Firstly, we refined the PBPK models of atorvastatin and atorvastatin lactone for predicting the DDIs with CYP3A4 and OATP inhibitors. Thereafter, we predicted the exposure changes of atorvastatin and atorvastatin lactone originating from the case reports of atorvastatin-induced rhabdomyolysis using the refined models. The simulation results show that pharmacokinetic DDIs of atorvastatin and its lactone with fluconazole, palbociclib diltiazem and cyclosporine are significant. Consequently, clinicians should be aware of necessary dose adjustment of atorvastatin being used with these four inhibitor drugs.

Diabetogenic effect of pravastatin is associated with insulin resistance and myotoxicity in hypercholesterolemic mice

BackgroundHMG-CoA reductase inhibitors (statins) are cholesterol-lowering drugs widely used to treat hypercholesterolemia and prevent cardiovascular disease. Statins are generally well tolerated, but adverse reactions may occur, particularly myopathy and new onset of diabetes. The exact mechanism of statin-induced myopathy and diabetes has not been fully elucidated. We have previously shown that treatment of hypercholesterolemic (LDLr−/−) mice with pravastatin for 2 months decreased pancreatic islet insulin secretion and increased oxidative stress and cell death, but no glucose intolerance was observed. The purpose of the current work was to study long-term pravastatin effects on glucose homeostasis, insulin sensitivity, muscle protein turnover and cell viability.MethodsLDLr−/− mice were treated with pravastatin for 3, 6 and 10 months. Glucose tolerance, insulin resistance and glucose-stimulated insulin secretion were evaluated. The rates of protein synthesis and degradation were determined in gastrocnemius muscle after 10 months of treatment. Insulin signalling, oxidative stress and cell death were analysed in vitro using C2C12 myotubes.ResultsAfter 6 and 10 months of treatment, these mice became glucose intolerant, and after 10 months, they exhibited marked insulin resistance. Reduced islet glucose-stimulated insulin secretion was observed after the 3rd month of treatment. Mice treated for 10 months showed significantly decreased body weight and increased muscle protein degradation. In addition, muscle chymotrypsin-like proteasomal activity and lysosomal cathepsin were markedly elevated. C2C12 myotubes exposed to increasing concentrations of pravastatin presented dose-dependent impairment of insulin-induced Akt phosphorylation, increased apoptotic markers (Bax protein and cleaved caspase-3) and augmented superoxide anion production.ConclusionsIn addition to reduced insulin secretion, long-term pravastatin treatment induces insulin resistance and muscle wasting. These results suggest that the diabetogenic effect of statins is linked to the appearance of myotoxicity induced by oxidative stress, impaired insulin signalling, proteolysis and apoptosis.

Association of SLCO1B1 and ABCB1 Genetic Variants with Atorvastatin-induced Myopathy in Patients with Acute Ischemic Stroke.

Certain patients experience muscle-related adverse effects after taking atorvastatin. Genetic factors play an important role in the occurrence of statin-induced myopathy. We aimed to identify genetic variants associated with statin-induced myotoxicity. We prospectively enrolled 1,102 acute ischemic stroke patients who underwent atorvastatin treatment for the first time after admission. Patients were separated into case and control groups after a follow-up of 3 months. We used a biochemical definition of myopathy consisting of serum creatine kinase values more than ten times the upper limit of normal for the reference laboratory (150 U/L). Fifty single nucleotide polymorphisms (SNPs) from seven genes of ABCB1, CoQ2, HTR3B, RYR2, CYP3A5, HTR7 and SLCO1B1 were selected and genotyped. The effects of genetic polymorphisms on myopathy were observed. 61 cases and 110 controls were recruited in the study. Compared with the controls, the cases had a significant higher mutant frequency of the allele A (ABCB1, rs2373588) (OR = 2.01, 95%CI = 1.10-3.67, P = 0.001) and a significant lower mutant frequency of the allele A (SLCO1B1, rs976754) (OR = 1.85, 95%CI = 1.12-3.03, P = 0.042). Genotypes or alleles of the other SNPs had no significant difference between the two groups (P > 0.05). Our findings reveal that SLCO1B1 and ABCB1 genetic variants are associated with statin-induced myopathy. These are valuable biomarkers for the evaluation of atorvastatin safety.

A Mechanism for Statin-Induced Susceptibility to Myopathy

This study aimed to identify a mechanism for statin-induced myopathy that explains its prevalence and selectivity for skeletal muscle, and to understand its interaction with moderate exercise. Statin-associated adverse muscle symptoms reduce adherence to statin therapy; this limits the effectiveness of statins in reducing cardiovascular risk. The issue is further compounded by perceived interactions between statin treatment and exercise. This study examined muscles from individuals taking statins and rats treated with statins for 4weeks. In skeletal muscle, statin treatment caused dissociation of the stabilizing protein FK506 binding protein (FKBP12) from the sarcoplasmic reticulum (SR) calcium (Ca2+) release channel, the ryanodine receptor 1, which was associated with pro-apoptotic signaling and reactive nitrogen species/reactive oxygen species (RNS/ROS)-dependent spontaneous SR Ca2+ release events (Ca2+ sparks). Statin treatment had no effect on Ca2+ spark frequency in cardiac myocytes. Despite potentially deleterious effects of statins on skeletal muscle, there was no impact on force production or SR Ca2+ release in electrically stimulated muscle fibers. Statin-treated rats with access to a running wheel ran further than control rats; this exercise normalized FKBP12 binding to ryanodine receptor 1, preventing the increase in Ca2+ sparks and pro-apoptotic signaling. Statin-mediated RNS/ROS-dependent destabilization of SR Ca2+ handling has the potential to initiate skeletal (but not cardiac) myopathy in susceptible individuals. Importantly, although exercise increases RNS/ROS, it did not trigger deleterious statin effects on skeletal muscle. Indeed, our results indicate that moderate exercise might benefit individuals who take statins.

The possible protective effects of vitamin D and L-carnitine against used atorvastatin-induced myopathy and hepatotoxicity

Statins are widely used antihyperlipidemic drugs. The occurrence of side effects mainly myopathy and hepatotoxicity leads to discontinuation of treatments with these drugs. It is suggested that these side effects are due to mitochondrial dysfunction, decreased antioxidant activity, and induction of inflammatory and apoptotic mediators. It was noticed that vitamin D and L-carnitine possess antioxidant activities and inhibit apoptotic protein expression. Statin-induced hepatotoxicity and myopathy was done by oral administration of atorvastatin (50 mg/kg/day) to rats. Other rats were treated with atorvastatin and vitamin D3 (500 IU/kg/day) or atorvastatin and L-carnitine (300 mg/kg/day). The administration of vitamin D3 and L-carnitine led to inhibition of oxidative stress in the liver and skeletal muscles providing a protective effect. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) increased by atorvastatin were significantly reduced by administration of vitamin D3 and L-carnitine. Histopathologically, vitamin D3 and L-carnitine administration provided a good protection for hepatic injury and muscle tissue against atorvastatin toxic effects. The use of vitamin D3 and L-carnitine produced a protective effect against atorvastatin-induced myotoxicity and hepatotoxicity. This protective effect was indicated by reduced oxidative stress and reduction of serum levels of ALT, AST, and CK.

Statin-Associated Bilateral Foot Myopathy

Objective: To report a case of statin-induced bilateral foot myopathy that resulted from 2 different statins. Case Summary: A 44-year-old Caucasian male with a history of ventricular fibrillation cardiac arrest, hyperlipidemia, and coronary artery disease experienced bilateral foot pain, weakness, and soreness while taking atorvastatin 20 mg daily. The pain subsided within weeks of discontinuing atorvastatin but returned years later after the initiation of rosuvastatin. The Naranjo probability scale indicates that this is a definite association between bilateral foot myopathy and statin use. Discussion: There is an association with statin use and lowering cardiovascular risk in patients with dyslipidemia and cardiovascular disease. However, statin metabolites can accumulate in the myocytes of muscle groups to cause a common side effect of myopathy. Statin myopathy typically occurs in large, bilateral, or proximal muscle groups, such as the thighs, back, calves, or buttocks. This patient was unusual in that his muscle symptoms only occurred in his feet and was severe enough to affect his ambulation. Conclusion: Stain-associated muscle symptoms have been reported to lessen medication adherence. There is also a risk with muscle symptoms that the patient could develop rhabdomyolysis, a rare but serious condition. Recognizing statin-associated muscle symptoms even in uncommon locations is important, so that alternative lipid-lowering strategies can be implemented to lower cardiovascular risk.

Statin Gene Testing: Revolutionary Tool to Increase Compliance and Care in Patients with Statin-Induced Myopathy

Statin Gene Testing: Revolutionary Tool to Increase Compliance and Care in Patients with Statin-Induced Myopathy

Pharmacogenomic Testing for Postoperative Pain Optimization Before Total Joint Arthroplasty: A Focus on Drug-Drug-Gene Interaction with Commonly Prescribed Drugs and Prior Opioid Use.

» Pharmacogenomic testing, together with early detection of drug-drug interactions, drug-gene interactions, and drug-drug-gene interactions prior to initiating pain management, can improve the selection of optimal opioid medication, and can reduce adverse drug interactions and therapeutic failures.» The ABCB1 gene and its variants influence pharmacodynamics by controlling plasma levels through limiting uptake or enhancing the clearance of commonly prescribed drugs.» Orthopaedic surgeons should pay close attention to drug-gene interactions in patients with the GG allele of ABCB1 (rs1045642) when these patients are being treated with opioids and simvastatin simultaneously. They will require higher doses of fentanyl, methadone, morphine, or oxycodone to achieve an optimal 24-hour pain response as well as be at higher risk of statin-induced myopathy.» Patients with the CC genotype of ABCB1 (rs2032582) polymorphism will require either alternatives to or higher dosages of tramadol to manage pain and rivaroxaban to achieve optimal venous thromboembolism prophylaxis following total joint arthroplasty.

C/EBP homologous protein deficiency inhibits statin‐induced myotoxicity

It has been well established that HMG‐CoA reductase inhibitors (statins) cause adverse side effects in skeletal muscle ranging from mild to fatal myotoxicity upon dose, drug interaction, and exercise. However, the underlying mechanisms by which statins induce myotoxicity have not been fully addressed. Recent reports showed that statins induce endoplasmic reticulum (ER) stress and cell death in immune cells and myoblasts in vitro. Therefore, the goal of study is to investigate the molecular mechanism by which statins induce skeletal muscle cell death and myopathy via the regulation of ER stress. Biochemical data showed that TUDCA, an ER stress inhibitor, inhibited atorvastatin‐ and simvastatin‐induced protein cleavages of PARP‐1 and caspase‐3, respectively. Actually, statin treatment activated marker proteins of unfolded protein responses (UPR) including ATF6, CHOP, and spliced XBP1 and these responses were inhibited by TUDCA. In addition, statin treatment induced mRNA levels of UPR marker genes, suggesting that statins activate ER stress in a transcriptional regulation. The physiological relevance of ER stress in statin‐induced myopathy was demonstrated in a mouse model of myopathy, in which instillation of simvastatin and atorvastatin led to myopathy. Notably, the reduction of muscular endurance in response to statin instillation was significantly improved in TUDCA treating group compared to vehicle control group. Moreover, CHOP deficiency mice showed restoration of statin‐induced reduction of muscular endurance, suggesting that statin induces myopathy via ER stress and in a CHOP‐dependent manner. Taken together, these findings indicate that statins specifically induce myopathy in an ER stress‐dependent manner, suggesting the therapeutic potential of ER stress regulation in preventing adverse effects of statin.Support or Funding InformationThis study was supported by the Medical Research Center Program (2015R1A5A2009124) and the Basic Science Research Program (2018R1A2B6004664) of the National Research Foundation of Korea funded by the Ministry of Science and ICT.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Does vitamin D supplementation prevent statin-induced myopathy?

Does vitamin D supplementation prevent statin-induced myopathy?

Genotyping of the OATP1B1 c. 521 T>C Polymorphism from the Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens: an Optimized Protocol.

Organic anion transporting polypeptide (OATP) 1B1 is a liver-specific transport protein that plays an important role in hepatic drug disposition. It transports many drugs from the blood into the liver, including lipid-lowering statins. The c. 521 T>C polymorphism of OATP1B1 has reduced transport activity and is associated with statin-induced myopathy. Formalin-fixed paraffin-embedded (FFPE) liver tissues can be an enriched source for genotyping of this clinically significant OATP1B1 polymorphism in retrospective studies. The successfulness of genotyping using Sanger-sequencing of a PCR product from FFPE tissue relies on a successful PCR amplification using genomic DNA extracted from the FFPE tissues. Such PCR amplification is often limited by the quality of DNA extracted from the FFPE tissue. An optimized method for high-quality DNA extraction and efficient PCR amplification is highly needed in order to genotype polymorphisms such as the c. 521 T>C polymorphism using FFPE tissues. The current study established an optimized and reproducible method for a Sanger-sequencing-based genotyping method using FFPE human liver tissues that is applicable to even small FFPE tissues such as needle-core biopsy specimens.

C/EBP homologous protein deficiency inhibits statin-induced myotoxicity

It has been well established that HMG-CoA reductase inhibitors (statins) cause adverse side effects in skeletal muscle ranging from mild to fatal myotoxicity upon dose, drug interaction, and exercise. However, the underlying mechanisms by which statins induce myotoxicity have not been fully addressed. Recent reports showed that statins induce endoplasmic reticulum (ER) stress and cell death in immune cells and myoblasts in vitro. Therefore, the goal of study is to investigate the molecular mechanism by which statins induce skeletal muscle cell death and myopathy via the regulation of ER stress. Biochemical data showed that TUDCA, an ER stress inhibitor, inhibited atorvastatin- and simvastatin-induced protein cleavages of PARP-1 and caspase-3, respectively. Actually, statin treatment activated marker proteins of unfolded protein responses (UPR) including ATF6, CHOP, and spliced XBP1 and these responses were inhibited by TUDCA. In addition, statin treatment induced mRNA levels of UPR marker genes, suggesting that statins activate ER stress in a transcriptional regulation. The physiological relevance of ER stress in statin-induced myopathy was demonstrated in a mouse model of myopathy, in which instillation of simvastatin and atorvastatin led to myopathy. Notably, the reduction of muscular endurance in response to statin instillation was significantly improved in TUDCA treating group compared to vehicle control group. Moreover, CHOP deficiency mice showed restoration of statin-induced reduction of muscular endurance, suggesting that statin induces myopathy via ER stress and in a CHOP-dependent manner. Taken together, these findings indicate that statins specifically induce myopathy in an ER stress-dependent manner, suggesting the therapeutic potential of ER stress regulation in preventing adverse effects of statin.

PGC-1β modulates statin-associated myotoxicity in mice

Statins inhibit cholesterol biosynthesis and lower serum LDL-cholesterol levels. Statins are generally well tolerated, but can be associated with potentially life-threatening myopathy of unknown mechanism. We have shown previously that statins impair PGC-1β expression in human and rat skeletal muscle, suggesting that PGC-1β may play a role in statin-induced myopathy. PGC-1β is a transcriptional co-regulator controlling the expression of important genes in mitochondrial biogenesis, antioxidative capacity and energy metabolism. The principle aim of the current study was to investigate the interaction between atorvastatin and PGC-1β in more detail. We therefore treated wild-type mice and mice with selective skeletal muscle knockout of PGC-1β (PGC-1β(i)skm-/- mice) with oral atorvastatin (5mg/kg/day) for 2weeks. At the end of treatment, we determined body parameters, muscle function, structure, and composition as well as the function of muscle mitochondria, mitochondrial biogenesis and activation of apoptotic pathways. In wild-type mice, atorvastatin selectively impaired mitochondrial function in glycolytic muscle and caused a conversion of oxidative type IIA to glycolytic type IIB myofibers. Conversely, in oxidative muscle of wild-type mice, atorvastatin enhanced mitochondrial function via activation of mitochondrial biogenesis pathways and decreased apoptosis. In PGC-1β(i)skm-/- mice, atorvastatin induced a switch towards glycolytic fibers, caused mitochondrial dysfunction, increased mitochondrial ROS production, impaired mitochondrial proliferation and induced apoptosis in both glycolytic and oxidative skeletal muscle. Our work reveals that atorvastatin mainly affects glycolytic muscle in wild-type mice and demonstrates the importance of PGC-1β for oxidative muscle integrity during long-term exposure to a myotoxic agent.

Statin-induced myopathy in muscles of lower limb with special reference to gastrocnemius muscle in albino rats

Statin-induced myopathy in muscles of lower limb with special reference to gastrocnemius muscle in albino rats

Statin-induced myopathy in muscles of lower limb with special reference to gastrocnemius muscle in albino rats

Statin-induced myopathy in muscles of lower limb with special reference to gastrocnemius muscle in albino rats

RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms.

To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls. Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls. 12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms. Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.

Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis.

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included. The summary ORs suggested that 521CC (OR: 2.31; 95% CI: 1.15-4.63; P = 0.019), 521TC (OR: 1.34; 95% CI: 1.02-1.76; P = 0.034), and 521CC + TC (OR: 1.82; 95% CI: 1.32-2.51; P < 0.001) were associated with a greater risk of statin-induced myopathy than 521TT. The higher incidence of statin-induced myopathy was found to be significantly correlated with the C allele compared with the T allele (OR: 1.89; 95% CI: 1.36-2.62; P < 0.001). In addition, we observed that 521CC + TC was associated with an increased risk of myopathy in individuals who received simvastatin (OR: 2.35; 95% CI: 1.08-5.12; P = 0.032) or rosuvastatin (OR: 1.69; 95% CI: 1.07-2.67; P = 0.024) when compared with 521TT. The 521C allele was associated with a greater risk of cerivastatin-induced myopathy than the T allele (OR: 1.95; 95% CI: 1.47-2.57; P < 0.001). The findings of this study indicated that SLCO1B1 T521C was associated with a significantly higher risk of statin-induced myopathy, especially for simvastatin, rosuvastatin, and cerivastatin. Future studies should be conducted in subjects receiving specific types of drugs, and any potential adverse events need to be explored.